Culmerciclib in HR+/HER2+ Advanced Breast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorSun Yat-sen University
About this trial
This is a phase II, multicenter, open-label, single-arm clinical study. The purpose of this study is to evaluate the efficacy and safety of culmerciclib combined with anti-HER2 targeted therapy and endocrine therapy as maintenance treatment in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer.
Culmerciclib is a novel oral cyclin-dependent kinase 2/4/6 (CDK2/4/6) inhibitor. It has been approved in China for use in combination with fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer who have progressed on prior endocrine therapy.
Patients enrolled in this study will receive culmerciclib at a stepwise escalating dose of 120 mg, 150 mg, and 180 mg once daily, in combination with anti-HER2 therapy (trastuzumab with or without pertuzumab) and physician-selected endocrine therapy. Treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, or loss to follow-up.
The primary endpoint is progression-free survival. Secondary endpoints include objective response rate, disease control rate, clinical benefit rate, overall survival, and safety.
Eligibility criteria
Qualifiers
Female patients aged 18 years and older with pathologically confirmed metastatic or locally advanced unresectable breast cancer.
Hormone receptor-positive and HER2-positive disease. HER2 positivity is defined as immunohistochemistry (IHC) 3+ or IHC 2+ with HER2 gene amplification confirmed by fluorescence in situ hybridization (FISH). If multiple tumor specimens have been tested, the most recent test result shall be used. Hormone receptor positivity is defined as estrogen receptor (ER) expression of at least 10%.
Patients must have available tumor tissue specimens for biomarker analyses including whole-exome sequencing.
Patients with brain metastases are eligible if they have asymptomatic central nervous system (CNS) metastases, defined as no CNS symptoms or symptoms are controlled and do not require urgent radiotherapy.
Disqualifiers
Patients with extensive leptomeningeal metastases that are poorly controlled with corticosteroids or other dehydrating agents, or requiring urgent radiotherapy.
Symptomatic active brain metastases requiring urgent cranial radiotherapy. Patients with asymptomatic CNS metastases are allowed.
Disease progression after whole-brain radiotherapy or stereotactic radiosurgery to all intracranial lesions.
Known spinal cord compression or active CNS metastases that have not been treated with surgery or radiotherapy, unless the condition has been stable for at least 1 month and corticosteroids have been discontinued for >2 weeks.
Trial design
Treatments tested in this trial
- Culmerciclib
Treatment groups
35 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov